AIM: To determine if brain-derived neurotrophic factor (BDNF) could offer protention to retinal ganglion cells following a superior colliculus (SC) lesion in mice using pattern electroretinogram (PERG) and opti...AIM: To determine if brain-derived neurotrophic factor (BDNF) could offer protention to retinal ganglion cells following a superior colliculus (SC) lesion in mice using pattern electroretinogram (PERG) and optical coherence tomography (OCT) as a measures of ganglion cell response and retinal health. METHODS: Seven C57BIJ6J mice with BDNF protection were tested with PERG and OCT before and after SC lesions, RESULTS: Compared with baseline PERG, the amplitude of PERG decreased 11.7% after SC lesions, but not significantly(P〉0.05). Through fast Fourier transform (FFT) analysis of the PERGs before and after SC lesions, it was found that dominant frequency of PERGs stayed unchanged, suggesting that the ganglion cells of the retina remained relatively healthy inspite of damage to the ends of the ganglion cell axons. Also, OCT showed no changes in retinal thickness after lesions. CONCLUSION: It was concluded that BDNF is essential component of normal retinal and helps retina keeping normal function. While retina lack of BDNF, ex vivo resource of BDNF provides protection to the sick retina. It implies that BDNF is a kind therapeutic neurotrophic factor to retina neurodegeneration diseases, such as glaucoma, age related macular degeneration.展开更多
The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across ...The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.展开更多
Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have b...Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12(P12), which is earlier than in the dLGN(P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN.展开更多
Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prer...Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.展开更多
Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients...Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.展开更多
Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the n...Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.展开更多
Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the r...Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual pathway.By applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole brain.Interestingly,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity.Furthermore,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic neurons.Thus,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual stimuli.These results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.展开更多
Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclea...Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.展开更多
Background: Manganese-enhanced magnetic resonance imaging (MEMR1) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium ...Background: Manganese-enhanced magnetic resonance imaging (MEMR1) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMR1. Methods: Forty New Zealand rabbits were divided into 0.05 mool/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n : 10 in each group). Each group was i-hrther subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. Results: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients ofMn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved ill the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2. were 5087 ~ 666 ng/ml, 22920 ± 1188 ng/ml ill the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular banier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.展开更多
文摘AIM: To determine if brain-derived neurotrophic factor (BDNF) could offer protention to retinal ganglion cells following a superior colliculus (SC) lesion in mice using pattern electroretinogram (PERG) and optical coherence tomography (OCT) as a measures of ganglion cell response and retinal health. METHODS: Seven C57BIJ6J mice with BDNF protection were tested with PERG and OCT before and after SC lesions, RESULTS: Compared with baseline PERG, the amplitude of PERG decreased 11.7% after SC lesions, but not significantly(P〉0.05). Through fast Fourier transform (FFT) analysis of the PERGs before and after SC lesions, it was found that dominant frequency of PERGs stayed unchanged, suggesting that the ganglion cells of the retina remained relatively healthy inspite of damage to the ends of the ganglion cell axons. Also, OCT showed no changes in retinal thickness after lesions. CONCLUSION: It was concluded that BDNF is essential component of normal retinal and helps retina keeping normal function. While retina lack of BDNF, ex vivo resource of BDNF provides protection to the sick retina. It implies that BDNF is a kind therapeutic neurotrophic factor to retina neurodegeneration diseases, such as glaucoma, age related macular degeneration.
基金This review was supported by the Key-Area Research and Development Program of Guangdong Province(2018B030331001)the National Natural Science Foundation of China(31630031 and 31930047)+3 种基金the Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence Fund(2019025),the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Chinese Academy of Sciences International Partnership Program(172644KYSB20170004)the CAS President’s International Fellowship for Distinguished Scientists(2021DB0003)the Canadian Institutes of Health Research(#10677).
文摘The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.
基金Project supported by the Shanghai Postdoctoral Scientific Program,the National Natural Science Foundation of China(No.31271158)the Doctoral Program of Higher Education from Ministry of Education of China+2 种基金the Innovation Program of Shanghai Municipal Education Commission(No.13ZZ002)the Shanghai Municipal Commission of Health and Family Planning,Science and Technology Commission of Shanghai Municipality(Nos.12ZR1441000 and 13PJ1401000)the Young 1000 Plan
文摘Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12(P12), which is earlier than in the dLGN(P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN.
基金supported by the National Natural Science Foundation of China(31771195,81790640 and 82021002)a Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)+1 种基金ZJLab,Key Scientific Technological Innovation Research Project of the Ministry of Education,Sanming Project of Medicine in Shenzhen(SZSM202011015)Shanghai Health and Family Planning Commission(20164Y0096,20184Y0184)。
文摘Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.
文摘Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.
基金supported by the National Natural Science Foundation of China, Nos.31830035, 91732304, 91632303, 81661148053, and 31771156(all to FQX)the Key-Area Research and Development Program of Guangdong Province of China, No.2018B030331001(to FQX)+4 种基金the SIAT Innovation Program for Excellent Young Researchers of China,No.E1G023(to FJ)the Guangdong Basic and Applied Basic Research Foundation of China, No.2021A1515011235(to FQX)Shenzhen Key Laboratory of Viral Vectors for Biomedicine of China, No.ZDSYS20200811142401005(to FQX)the National Basic Research Program(973 Program)of China, No.2015CB755600(to FQX)the Strategic Priority Research Program(B)of China, No.XDB32030200(to FQX)
文摘Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.
基金supported by grants from the National Key R&D Program of China(2017YFE0103400)the National Nature Science Foundation of China(81470628).
文摘Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual pathway.By applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole brain.Interestingly,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity.Furthermore,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic neurons.Thus,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual stimuli.These results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.
基金the National Key Research and Development Program of China(2018YFA0108503)the National Natural Science Foundation of China(81760251 and 81560234)the Yunnan Provincial Natural Science Foundation(2018FB118 and KKSY201626001).
文摘Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.
文摘Background: Manganese-enhanced magnetic resonance imaging (MEMR1) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMR1. Methods: Forty New Zealand rabbits were divided into 0.05 mool/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n : 10 in each group). Each group was i-hrther subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. Results: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients ofMn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved ill the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2. were 5087 ~ 666 ng/ml, 22920 ± 1188 ng/ml ill the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular banier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.